The identity and topographic localization of cells and their markers in patient samples and various experimental uveitis animal models were analyzed by immunohistochemistry, in situ hybridization, polymerase chain reaction (PCR), and microdissection. In FY1999 we have complished the following 4 research topics: 1. Detection of Genes and Proteins in Primary Intraocular Lymphoma Cells. Using microdissection and PCR techniques we linked the presence of some infectious agents and primary intraocular lymphoma. We further reported the association between B-cell lymphoma, intravitreal IL-10 level and IL-10:IL-6 ratio and that could improve the diagnostic yield for this tumor.2. HTLV-1 Infection and T cell leukemia/lymphoma. Using microdissection and PCR, we studied and demonstrated HTLV-1 viral genes and T cell receptor gene rearangements in HTLV-1 associated T-cell leukemia/lymphoma. 3. Pathogenesis of Endotoxin-Induced Uveitis (EIU). Using ELISA and RT-PCR, we studied the kinetics of cytokines and pathology in murine EIU. We found that the disease is closely related to various cytokine levels, particularly IL-6, in the eye. Ocular inflammatory response to LPS is biphasic in the most susceptible strain, C3H/HeN. In contrast, ocular inflammation is monophasic without two cytokine waves in other murine strains with EIU. 4. Modulation of Allergic Conjunctivitis. We showed that immunostimulatory DNA sequences (ISS) can inhibit an on-going Th2/allergic response and induce a de novo Th1 response in the ragweed (RW)-induced murine allergic conjunctivitis model. Systemic or topical ISS after RW sensitization inhibits both immediate hypersensitivity response and the late-phase cellular infiltration and induced a RW-specific Th1 response. ISS may provide an alternative to the current standard care of ocular allergy.